Medical implant

ABSTRACT

The invention relates to a medical implant, in particular a dental implant, intended for implantation in available cavities. Dental implants are implanted in extraction sockets. The implant is provided with reservoirs for a biologically active substance. An advantage of the implant is that, for dental procedures, it can be manufactured and implanted as part of a single therapeutic treatment. However, the implant can also be used as a release system for biologically active substances.

This application was filed as international patent applicationPCT/EP96/05506 on Dec. 10, 1996.

INTRODUCTION AND BACKGROUND

The present invention concerns a medical implant that is intended to beinserted into a space with a prespecified dimension and to be filled anda process for producing the medical implant.

It is known that in cases of extraction wounds bones change in such away that the space that exists due to the extraction wound can no longerbe filled by an implant whose dimension and shape corresponds exactly tothe extracted hard connective tissue after a certain time period.

A loss of a tooth that arises through a trauma when the tooth isunfavorably fractured and the root fragments cannot be saved can bementioned as an example. Consequently, one must extract the fracturedtooth and its root fragments. As a replacement one has been using abridge or removable prothesis for a long time. They have thedisadvantage of involving the neighboring teeth during anchoring, and ifnecessary, of having to be worked on. To eliminate this disadvantage onesometimes uses immediate implants instead of the lost tooth. Because upto now they have only consisted of prefabricated, standardizedalloplastic materials, the extraction sockets cannot be filled by theimmediate implants, which must exactly match. As a result, hollow spacesnecessarily exist between the end of the socket and the implant. Duringthe healing process these hollow spaces are filled by quickly growingconnective tissue, which prevents the complete osseo-integration of theprefabricated, standardized implants. Therefore a large share of theimmediate implants that have been used up to now is again lost.

As one knows, the consequence for the loss of a tooth is the atrophy ofthe bone in the area of the extraction socket. All bone loss in the jawarea is extremely unfavorable for the subsequent replacement of the losttooth. Through the loss of bone volume a later implantation of asynthetic tooth root--i.e., an enossal implant--becomes difficult.Because even when the extraction wound undergoes a normal healingprocess some substance from the jaw bone in the area of the jaw ridge islost, it is impossible to place the implant in the position thatcorresponds exactly to that of the extracted tooth and its root.Compared with the original natural position, such an implant has beenstrongly shifted on a horizontal and vertical level. This fact hasunfavorable aesthetic and practical effects.

Implants can also be used as a replacement for other parts of theskeleton. If, for example, the lower jaw is stricken by a tumor, thearea stricken by the tumor is separated from the jaw bone and replacedby an implant. In this case as well the difficulties mentioned aboveoccur.

SUMMARY OF THE INVENTION

The present invention is based on the technical problem of shorteningthe time between the loss of the hard connective tissue associated withtherapy--e.g., loss of bone substance, especially after the extractionof a tooth has occurred--and the insertion of an implant in such a waythat bone loss of a notable dimension cannot occur.

The present invention is especially based on the technical problem ofcarrying out a single therapeutic treatment of the hard connectivetissue as a result of a bone resection, especially with the requiredextraction of a tooth, and the insertion of an exactly matchingindividual implant in the sense of a so-called "custom-made system" atthe intended site.

This problem is solved by the present invention, which concerns amedical implant for insertion into a space with a prespecifieddimension--e.g., the extraction socket--and a process for producing thisimplant.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Cast cavity in the form of an impression of the root of a tooth,with inserted mandrels

FIG. 2: Cast cavity filled with biodegradable material, with analternative arrangement of the mandrels

FIG. 3: Implant with the mandrels not yet removed

FIG. 4: Implant according to FIG. 1, which is inserted into the jaw boneand which has reservoirs with biologically active substances that arisein place of the mandrels and that are filled

FIG. 5: Part of the lower jaw to illustrate another working example ofthe invention

FIG. 6: Moulding material that contains the mandrels for formingreservoirs and that is filled with a biodegradable material to form oneof the implants corresponding to the resection defect

FIG. 7: Implanted implant with filled reservoirs

FIG. 8: Lower jaw with implant affixed to it

FIG. 9: Cut through an implant core serving as a fixture according toanother working example of the invention

FIG. 9A: Section of FIG. 9 with a variation of a structured inner sideof the implant core according to FIG. 9:

FIG. 10: View onto the implant core according to FIG. 9

FIG. 11: Washer

FIG. 12: Filament-shaped mandrel

FIG. 13: Mandrel with smoothbare shaft and head with screw thread

FIG. 14: Implant core according to FIG. 9 with inserted mandrel

FIG. 15: Implant core according to FIG. 14 inserted into the impressionin the moulding material

FIG. 16: Implant core according to FIG. 15 with filled reservoirs

FIG. 17: Screw cover

FIG. 18: Inserted implant with reservoirs closed by a screw cover

FIG. 19: Another working example of an implant core

FIG. 20: Implant core according to FIG. 9 with an inner space partiallyfilled with biodegradable material

FIG. 21: Implant core for inserting in moulding material

FIG. 22: Cast cavity filled with biodegradable material, with fixture

FIG. 23: Finished implant

FIG. 24: Implanted implant

FIG. 25: Another working example of an implant core with mandrels

FIG. 26: Implant core according to FIG. 25 inserted into mouldingmaterial and

FIG. 27: Implant with an implant core in accordance with FIG. 25.

DETAILED DESCRIPTION OF THE INVENTION

The object of the invention is a medical implant 5 for insertion into aspace with a prespecified dimension and for filling a cast cavity 2 witha hardening plastic material with mineral components on a basis ofcalcium and phosphate or, in the case of the new formation of bone, abiodegradable material, or a combination of both, characterized by thefact that

a) at least one mandrel 3, or 23, 24, is placed in the cast cavity 2 insuch a way that it can be removed from the cast cavity 2 of the formedimplant 5 after the plastic material hardens and creates a space 6 or 19(after its removal) that extends from the inner area of the implant 5 toits outer surface, thus forming a reservoir that can be filled with abiologically active substance, or

b) the cast cavity 2 contains a porous matrix with a biologically activesubstance, and the hollow spaces of this matrix are filled with thehardening plastic material.

Preferably, the invention concerns tooth implants or tooth rootimplants. The implant has, for example, the advantage that with dentalsurgery, producing and implanting the individual implant can be carriedout as a single therapeutic treatment. As a result, time can be savedand a traumatic second operation prevented. A second anesthesia is notnecessary; nor is the added stress to the patient of another "surgery."The implantation treatment can be carried out outside of dental clinicsin private practices by dentists with normal training. A high acceptanceamong patients can be obtained because the loss of connective tissue canbe replaced immediately and with little risk. By producing and insertingthe individual transplant immediately, alveolar bone loss can beprevented. Other bone fragments can also be replaced with an exactlymatching, biocompatible, biodegradable fitted body, which contains afixture made of alloplastic material in specific designs. The object ofthe variations of the invention is illustrated in greater detail belowwith the use of drawings.

The process for producing the medical implant 5 is also an object of theinvention and is characterized by the fact

α) that one forms a cast cavity 2 in the form of an impression of theextracted tooth or the resected bone; that one fills this cast cavity 2with a hardening material with mineral components on the basis ofcalcium and phosphate or, in the case of the new formation of bone, abiodegradable material; that one places at least one mandrel 3, or 23,24, in the cast cavity 2 in such a way that it can be removed from thecast cavity 2 of the formed implant after the plastic material hardensand with the removal of the mandrel a space 6, or 19, forms that servesas a reservoir and extends from the inner area of the implant 5 to itsouter surface; and that one fills the reservoir with a biologicallyactive substance after removing the mandrel 3, or 23, 24, or

β) that one forms a cast cavity 2 in the form of an impression of theextracted tooth or the resected bone; that one fills the cast cavity 2with a porous matrix that contains a biologically active substance andthe hollow spaces of this matrix with the hardening plastic material.

Also an object of the invention is a nontherapeutic process forproducing the medical implant 5, which is carried out outside of a humanor animal's body and is characterized by the fact

α') that one forms a cast cavity 2 in moulding material 1 in the form ofan impression of the extracted tooth or the resected bone; that onefills this cast cavity 2 with a hardening material with mineralcomponents on the basis of calcium and phosphate or, in the case of thenew formation of bone, a biodegradable material; that one places atleast one mandrel 3, or 23, 24, in the cast cavity 2 in such a way thatit can be removed from the cast cavity 2 of the formed implant after theplastic material hardens and with the removal of the mandrel forms aspace 6, or 19, serving as a reservoir, that extends from the inner areaof the implant 5 to the outer surface; that one removes the formedimplant 5 from the cast cavity and fills the reservoir with abiologically active substance after the removal of the mandrel 3, or 23,24, or

β') that one forms a cast cavity 2 in moulding material 1 in the form ofan impression of the extracted tooth or the resected bone; that onefills the cast cavity 2 with a porous matrix that contains abiologically active substance and the hollow spaces of this matrix withthe hardening plastic material and removes the formed implant 5 of thecast cavity.

An especially preferred variation of the procedure is characterized bythe fact that one first places in the cast cavity 2 several mandrels 3,or 23, 24, that extend from the cast cavity 2 into the moulding material1 and are placed in the moulding material 1 in such a way that one canremove the mandrels 3, or 23, 24, from the implant after pouring theplastic moulding material into the cast cavity 2, letting it harden, andthen removing the formed implant 5 from the cast cavity 2.

The invention will be further understood by the following Examples:

EXAMPLE 1

In FIGS. 1-4 a first working Example of the invention and its productionprocess is illustrated, whereby the implant fills a bone defect that hasarisen from the extraction of a tooth.

FIG. 1: At first the involved tooth is extracted. If there is afracture, its fragments--especially the root--are agglutinated. Thecontaminated root surface of the tooth is cleaned aseptically,mechanically, and/or chemically. The tooth is then pressed into mouldingmaterial 1 up to the tooth neck by a known method; the moulding materialis a sterile, elastic moulding compound of a known type such asalginates, silicone cross-linked with additives and condensation,polyether, etc. After the moulding material 1 hardens, the tooth istaken out, and a cast cavity 2 in the form of an impression of thedental implant to be produced is formed in the moulding material 1.

Several mandrels 3 in the form of filaments or rods made of smoothmaterial that resists breakage are inserted from the cast cavity intothis moulding material. The term mandrel includes objects and devicesthat are used as place holders for reservoirs or hollow spaces that canbe filled. The filament- or rod-shaped mandrels 3 are placed in such away that they do not reach the level 4 of the limbus alveolaris. As aresult, a cast cavity 2 in which the mandrels 3 are arranged as shown inFIG. 3 is formed in the moulding material 1.

This cast cavity 2 is then filled with a hardening plastic material withmineral components on the basis of calcium and phosphate or, in the caseof the new formation of bone, a biodegradable material, or a combinationof the two.

Plastic materials with mineral components on the basis of calcium andphosphate (CPHC: calcium phosphate hydraulic cements) can be obtained bycombining partly neutralized phosphate materials and calcium salts inaccordance with the procedure described in European patent application416 761. Suitable phosphate materials are, for example, Ca(H₂ PO₄)₂.H₂ O[MCPM], CaHPO₄.H₂ O [DCPD: brushite], Ca₉ (HPO₄).(PO₄)₅ (OH) [CDHA:calcium-deficient hydroxyapatite], Ca₃ (PO₄)₂ [α- or β-tricalciumphosphate: TCP], Ca₅ (PO₄)₃ (OH) [OHAP: hydroxyapatite], Ca₂₈ (PO₄)₁₅(CO₃)₃ (OH)₅ [CHAP: carbonated hydroxyapatite], Ca₂ P₂ O₇ [CPP: calciumpyrophosphate], CaSO₄.0.5H₂ O [CHS: "Plaster of Paris"], CaSO₄.2H₂ O[CSD: plaster], CaCO₃ [CC: calcite], or mixtures thereof.

Preferred is a plastic material with mineral components on the basis ofcalcium and phosphate with the following shares: 60-80% β-TCP, 40-20%MCPM, an aqueous solution containing P₂ O₇ ⁴⁻ and SO₄ ²⁻ ions andadditives of the cellulose ether type, for example, HPMC (0.5-1.0%) orpolysaccharides.

Materials suitable for the new formation of bone have osteo-conductiveproperties and are preferably biodegradable and biocompatible.Osteo-conductive materials control the make-up of a structure for thenew formation of bone during "guided bone repair" (GBR).

Biodegradable and biocompatible materials are generally known--e.g.,aliphatic polyesters of the types polyglycolic acid (PGA) or polylacticacid (PLA) and their compounds (PGA/PLA); enantiomeric forms and racemiccompounds in various proportions, e.g., poly-L-lactate (PLLA),poly-D-lactate (PDLA), poly-DL-lactate (PDLLA), L-lactate/DL-lactate, orL-lactate/D-lactate. These materials are not only biodegradable, theyare also biocompatible. PGA and PLA have metabolism channels (pathways)in the human body. Furthermore, PGA and PLA materials are notimmunogens--that is, these materials do not cause immune reactions inmammals. Suitable materials are, for example, commercial products of thetype Biofix®, which can be obtained commercially from the firmBioscience (SF-33721 Tampere).

Suitable aliphatic polyesters with osteo-conductive properties are, inaddition, PLA copolymers, e.g., lactate/tetramethyleneglycolidcopolymers, lactate/trimethylene carbonate copolymers,lactate/α-valerolactone copolymers, lactate/ε-caprolactam copolymeres,polydepsipeptide (glycine-DL-lactate copolymers or PLA/ethylene oxidecopolymers (PLA/PEO)), polylactide-polyglycolid copolymers orpolylactide-ethylene oxide copolymers or polyhydroxyalkanoates, e.g.,PHB [Poly(β-hydroxybutyrate)], PHB/PHA(polyhydroxybutyrate/polyhydroxyvalerate), PCL [poly(ε-caprolactam), PDS[poly(p-dioxanone)], polyanhydrides, polyhydroxysuccinic acid (β) orpolyhydroxysuccinic acid ester.

Suitable materials for the new formation of bones that haveosteo-conductive properties are, in addition, vinyl polymers, e.g., onthe basis of polyvinyl alcohol (PVA), poly-β-maleic acid, aliphaticpolyamides, aliphatic polyurethanes, e.g., polyurethanes made ofpolyethyleneglycol-(PEG)-diols or polycaprolactam-diols anddiisocyanates such as 1,4-methylene diisocyanate, polyorthoesters, e.g.,of the type Alzmer® (Alza Corp.) or DETOSU, aliphatic polyanhydrides,polypeptides, e.g., synthetic polyamino acids and poly-α-amino acids,e.g., poly-β-lysine or polybenzylglutamate, polyphosphates,polysaccharides, e.g. dextran derivatives, chitin derivatives, andchitosan derivatives or hyaluronic acid esters, modified proteins, e.g.,cross-linked collagen or fibrin, or modified carbohydrate polymers.

Also suitable are their composites and the block and graft copolymers ofthe polymers and copolymers mentioned.

The plastic materials named can be put into place in the cast cavity 2by using suitable filling instruments, e.g., injection instruments.

FIG. 2: FIG. 2 shows a cast cavity, filled with biodegradable material,that has taken the form of the implant 5 after the plastic material hashardened. Compared with the model in FIG. 1, the mandrels 3 here have analternative arrangement and design.

FIG. 3: After the materials for implant 5 have hardened it is removedfrom the cast cavity 2 together with the mandrels 3. Then thefilament-shaped mandrels 3 are pulled out of the implant 5. In this way,channel- and capillary-shaped spaces or gaps 6 are formed in the implant5, which serve as reservoirs for biologically active substances(so-called active substances).

Suitable biologically active substances are poured into the reservoirs.They have osteo-conductive properties and can have an effect on thebiological behavior of neighboring cells, for example, by stimulatingthe division of cells or the formation of bone, through, e.g., theformation of mesenchymal cells, endothelial tissue, pericytes,osteoclasts, osteoblasts, etc. Suitable biologically active substanceswith osteo-conductive properties are, for example, hormones, proteins orgrowth factors on a protein or lipid basis that are known by such namesas epidermal growth factor (EGF); vascular epidermal growth factor(VEGF); fibroblast growth factor (FGF); platelet derived growth factor(PDGF); transforming growth factor-β(TGF-β), e.g., of the type TGF-β-1,TGF-β-2, or TGF-β-3; insulin-like growth factor (IGF-I and IGF-II);nerve growth factor (NGF); bone morphogenic proteins (BMP), e.g., BMP-3(osteogenin), BMP-2 (BMP 2A), BMP-4 (BMP 2B), BMP-5, BMP-6, BMP-7(osteogenic protein-1); and proteins that are known by the namesparathyroid hormone (PTH), e.g., PTH fragments such as FTH 1-34 and itsderivatives; parathyroid hormone related proteins (PTHrP), e.g., PTHrPfragments, e.g., PTHrP 1-34 and its derivative osteoglycin, cartilageinduction factor and skeletal growth factor. Bone growth factors on alipid basis include prostanoids, which are known by the namesprostaglandins A, D, E, F, I and derivatives of them such asprostacyclin.

Proteins (active components) with the properties of a transformed growthfactor of type beta (TGF-β) are known and described in the surveyarticle from A. B. Roberts and M. B. Sporn, "The Transforming GrowthFactor-βs," in the Handbook of Experimental Pharmacology: Peptide GrowthFactors and Their Receptors, edited by M. B. Sporn and A. B. Roberts.New York: Springer Verlag, pp. 419-72.

Proteins of the type TGF-β of human origin are known and described inthe survey article by D. A. Cox, "Transforming Growth Factor-Beta 3."Cell Biology International 19, no. 5 (1995): 357-71.

Recombinant proteins of type TGF-β are known and described in thefollowing survey article: Lionel Bourdel, et al. "Recombinant HumanTransforming Growth Factor-β1: Expression by Chinese Hamster OvaryCells, Isolation and Characterization." Protein Expression andPurification 4 (1993): 130-40; M. P. Schlunegger and M. G. Grutter. "AnUnusual Feature Revealed by the Crystal Structure at a Resolution ofHuman Transforming Growth Factor-β 2." Nature 358 (1992): 430-34; S.Runser and N. Cerietti. "Transforming Growth Factors β: ConformationalStability and Features of the Denaturation of Recombinant HumanTransforming Growth Factors-β 2 and β 3." Biotechnol. Appl. Biochem. 22(1995): 39-53.

Proteins with the properties of a transforming growth factor of typebeta (TGF-β) chosen from the group consisting of TGF-β 1, TGF-β 2, TGF-β3, and TGF-β 5 and bone-morphogenic proteins (BMP) are known anddescribed in the survey article by D. M. Kingsley, "The TGF-βSuperfamily: New Members, New Receptors, and New Genetic Tests ofFunction in Different Organisms." Genes and Development 8 (1994):133-46.

Additional substances that can be poured into the reservoirs mentionedare active substances that inhibit bone resorption, e.g.,bisphosphonates of the type Aredia®, nitrates, e.g., nitroglycerin,ipriflavon, active substances that bind with nuclear receptors such asestradiol, enzyme inhibitors that block enzymes that break down the bonematrix, collagenase inhibitors, stromelysine [Stromelysin] inhibitors,cathepsin L, K inhibitors, substances that inhibit osteoclast functionssuch as carboanhydrase inhibitors or inhibitors of the osteoclasticproton pump, etc.

Other active substances are those that are effective againstinplantopathogens (paradontophathogens), e.g., antibiotics, antibodies(monoclonal, polyclonal), inflammation inhibitors, prostaglandininhibitors, active substances with immune-suppressive effects such as(bio)synthetic immune suppressors, active substances withrevascularization-promoting effects such as vascular-forming substances,active substances that promote circulation, or analgesics. Beforeinserting the implant, one pours the biologically active substances thatare to be dispensed, or combinations of such substances, into thereservoir 6. The biologically active substances mentioned, for example,can be poured into the reservoirs by using traditional medical injectioninstruments.

The implant filled with the biologically active substance represents a"dispensing unit," which contains a dose of the substance to bedispensed and releases it within a set time period. A dispensing unit asdefined here contains one dose of the substance to be dispensed, or afaction or multiple of it. It can be dispensed spontaneously, e.g., bydiffusion or erosion of the system through interaction with body fluids.

FIG. 4: One places the exactly matching implant 5 in the socket in thejaw bone 7, whereby in FIG. 4 the gingiva 8 is also implied. In so doingthe substances 9 are released from the implanted implant.

EXAMPLE 2

Another working example of the invention that is especially well suitedfor use as a dispensing unit is represented in FIGS. 5-9.

FIG. 5: FIG. 5 shows a lower jaw 10 in which a tumor 11 has formed. Thebone part 12 stricken with the tumor 11 is removed from the lower jaw 10and then an impression is made in the moulding material 1 (see thesection according to FIG. 6). The mandrels 3 are placed in the castcavity 2 so their ends project out of the moulding material 1. Thearrangement of the mandrels 3 shown in FIG. 6 is reproduced as anexample and can vary. After inserting the mandrels 3, the cast cavity 2is filled with the biodegradable material that hardens into an implant5.

FIG. 6: The bone part 12 removed from the lower jaw 10 according to thedrawing in FIG. 6 is pressed into the moulding material 1 and rotated by180° compared to the drawing in FIG. 5 so that the upper, roundedsection of the bone part 12, in accordance with the drawing in FIG. 6,is located at the bottom as shown in FIG. 6. The remaining spaces orreservoirs 6 in the implant 5 after removing the mandrels 3, asdescribed above, are filled with one or several active substances 9.

FIG. 7: The implant 5 is implanted into the intended site in the lowerjaw 10, as is shown in FIG. 7.

FIG. 8: If necessary, one can attach the implant 5 by using a plate 13in the jaw bone, whereby the plate 13 as well as the screws 14 belongingto it can also consist of a biodegradable material.

EXAMPLE 3

With the use of FIGS. 9-18 another working example of the invention isdescribed.

FIG. 9: FIG. 9 shows a sectional view of an implant core that alsoserves as a fixture. The term fixture designates the enossal part(inside the jaw bone) of an implant, which takes up the part of animplant construction (the visible part of the implant) projecting fromthe jaw bone. Such an implant core consists of an alloplastic,osseo-integratable material, e.g., titanium, Frialit, etc. It has theform of an elongated hollow body 18 with an inner space 15. Its outerside is structured, for example, in the form of a screw thread 16. Otherdesigns also provide for a structuring of the inner side. An insidescrew thread 17 is designed at the upper end of the inner space 15. Inthe wall of the hollow body 18 hollow spaces 19 that run parallel to theinner space 15 exist and are open at the top and closed at thebottom--i.e., at the end far away from the inside screw thread 17.Another arrangement of the hollow spaces 19 is possible as analternative to the parallel arrangement to the inner space 15. As isclear from FIG. 9, the hollow body 18 is tapered to the lower end, i.e.,to the root tip. The inside screw thread 17 at the upper wider end,i.e., in the area of the limbus alveolaris, not only serves to seal thereservoir of active substances, as will be described later, but also toattach the suprastructure later when the tooth is restored or to attachthe prosthesis with help of the implant. The hollow spaces 19 in thewall of the hollow body 18 are arranged in such a way that they cut thegrooves of the screw thread 16 or the respective structure of the wallof the hollow body 18. Moreover, perforations 20 exist in the wall thatrun from the hollow spaces 19 to the outer surface of the hollow body.

FIG. 9A: An alternative arrangement of the perforations is shown in FIG.9A, which represents a cut from FIG. 9. In this design the inner surfaceof the hollow body 18 is also structured. In this connection additionalperforations 20A, which run from the hollow spaces 19 to the innersurface of the hollow body 18, exist and connect the hollow spaces 19with the inner space 15 of the hollow body 18. A design is also providedin which only the inner surface of the hollow body 18 is structured.

FIG. 10: FIG. 10 represents the view onto the implant core in accordancewith FIG. 9.

FIG. 11: FIG. 11 shows a packing ring 21 that is intended for insertioninto the upper, recessed end section 22 of the hollow body 18. Thispacking ring 21 can consist of silicone rubber or soft gold or plasticsealing metal beads so that, with the packing ring 21 inserted into thearea 22 A, the openings to the hollow spaces 19 and the hollow space 15are safely closed off to outside influences, e.g., the penetration ofpathogens (bacteria, yeasts, viruses, etc.).

FIG. 12: FIG. 12 shows a filament-shaped mandrel 23. Its diameter iscalculated in such a way that it can be inserted into a respectivehollow space 19.

FIG. 13: In FIG. 13 another mandrel 24 is designed that consists of ashaft 25 and a head 26 that has an exterior screw thread 26 A and a slit27 at the top for accommodating a screwdriver like tool.

FIG. 14: To produce an implant, first the mandrel 24, which has a shaft25 and head 26, is screwed into the inner space 15 of the hollow body18. Then the filament-shaped mandrels 23 are inserted into therespective hollow spaces 19. In a first step, a first amount of aplastic biodegradable material is placed in the inner space 15 frombelow in the direction of arrow A.

FIG. 15: An impression of the root of the tooth to be replaced by theimplant--that is, the cast cavity 2--is produced in the mouldingmaterial 1. In a second step, a second amount of the biodegradablematerial is poured into the cast cavity; and in a third step the hollowbody 18, already filled and equipped with the mandrels 23 and 24, ispressed into the still liquid biodegradable material. To pour it thebiodegradable material is liquified by warming it (in specialapplication syringes or another way) depending on its composition, or itis available in liquid or plastic form at room temperature. Thickeningand hardening ensues either by cooling the thermoplastic material orthrough a chemical reaction (e.g., a 2-component reaction, aphotochemical process, or polymerization, etc.). It is clear from FIG.15 how the gap between the outer wall of the hollow body 18 and theinner wall of the cast cavity 2 in the moulding material 1 is filled bythis material. After the material hardens, the implant 5, in which thehollow body 18 that still has the mandrels 23 and 24 is imbedded,exists. The implant 5 is removed from the moulding material 1 and thenthe filament-shaped mandrels 23 and the mandrel 24 are pulled andscrewed out, respectively, of the implant 5.

FIG. 16, FIG. 17: The biologically active substances described earliercan be poured into the remaining spaces 6. The spaces 6 are closed offat the top by the screw cover 28 (FIG. 17). In this way an implant 5 isformed that has an alloplastic fixture (hollow body 18) on the inside,which is surrounded by a biodegradable material. Reservoirs 19, 15 foractive substances exist. The implant, anatomically replicated tocorrespond to the extracted root, is ready to be placed in theextraction socket.

FIG. 18: FIG. 18 shows the implant 5 inserted into the jaw bone 7,whereby the gingiva is also shown. The packing ring 21, which closes offthe inner spaces to outside influences such as bacteria, is positionedbetween the screw cover 28 and the hollow body 18.

The implant 5 fits exactly in the extraction socket, and the healingprocess can follow per primam through the close contact to thesurrounding bones. The biodegradable material begins to reabsorb. Whenthe reservoirs are opened due to the biodegradation process, the resultis the release of the growth factors and/or active substances. Thisleads to the accelerated, controlled new formation of bone and aqualitatively optimized osseo-integration of the alloplastic implantcore.

EXAMPLE 4

Another design is described below with reference to FIGS. 19-24.

FIG. 19: The hollow body 18, which consists of an osseo-integratablematerial, has an inner space 15 in the middle. Along the structuredouter wall run elongated hollow spaces 19 corresponding to the workingexample described above. The hollow spaces 19 cross the grooves of thestructured outer wall so that perforations 20 are formed that create aconnection between the hollow spaces 19 and the outer surfaces of thehollow body 18. On the inner wall of the inner space 15 additionalopenings or perforations 29 to the outer surfaces are designed, wherebysuch openings 29 also exist in other working examples. The hollow body18, which later serves as a fixture, has a screw thread 30 at the top,into which a temporary screw cover 31 can be screwed, whereby the screwthread 30 later serves as a means of affixing the tooth construction.

A rod-shaped mandrel 24 A with a handhold that ends in a handle 32, isstuck in the inner space 15 from below. Filament-shaped mandrels 23 A,which have a tip 33 at the lower end, are stuck in the hollow spaces 19running along the outer wall.

FIG. 20: As a first step, biodegradable material is injected from thelower opening 34 and through the openings 29 into the annulus betweenthe mandrel 24 A and the inner wall of the hollow body 18. After thematerial hardens, the mandrel 24 A is pulled out so that a layer 35 ofthe biodegradable material exists in the inner space 15.

FIG. 21: A first amount of the active substances 9 mentioned is pouredinto the hollow space 6, and the hollow space 6 is closed with apeg-shaped seal 36. The seal 36 also consists of the biodegradablematerial.

FIG. 22: The impression of the root of the tooth to be replaced isproduced in the moulding material 1 by the known method--i.e., the castcavity 2 is formed. The biodegradable material is poured into the castcavity 2 and then the implant core is inserted into the cast cavity 2 inaccordance with FIG. 21, whereby the tips 33 of the filament-shapedmandrels 23 penetrate the moulding material 1.

FIG. 23: After the poured, biodegradable material thickens and hardens,the formed implant 5 is removed from the cast cavity 2 and thefilament-shaped mandrels 23 A are pulled out of the implant core frombelow and the respective medical substances poured into the availablespaces 19. The lower openings 37 of the filled spaces 19 are thenclosed. For this purpose, warmth caused by friction can be produced byusing a rotating dental instrument, e.g., a rose-head burr, in the areasof the openings 37 so the biodegradable material melts at these sitesand the openings 37 are closed.

FIG. 24: The finished implant 5 can then be implanted in the extractionsocket in accordance with the diagram in FIG. 24.

EXAMPLE 5

With the use of FIGS. 25-27 another working example is described. Thesteps in the procedure are analogous to those already described. Thusthe process will be described below in simplified form.

FIG. 25: The hollow body 18 or implant core is analogous to the workingexample in accordance with FIG. 19. The rod-shaped mandrel 24, however,does not end in a handle; it ends in a tip 38.

FIG. 26: After the cast cavity 2 in the moulding material 1 is filledwith the biodegradable material, the hollow body 18 is inserted into thecast cavity 2, whereby all of the tips 33, 38 of the mandrels 23, 24 arestuck into the moulding material. After the biodegradable materialthickens and hardens, the mandrels 23, 24 are pulled out of the implant5 from below and the existing spaces--the reservoirs--are filled withthe corresponding medical substances. Then the inner space 15 is closedby the peg-shaped seal 36 and the spaces 19 running along the outer sideof the implant core by the lower openings 37 are welded together byfrictional heat so that the implant is obtained in accordance with FIG.27.

FIG. 27: Finished implant with an implant core in accordance with FIG.25.

In another variation that is not shown in the diagrams, one places amandrel in the cast cavity 2, which runs vertically from the uppersurface to the lowest point in the cast cavity 2. The mandrel is placedin the moulding material 1 in such a way that--after pouring the plasticmaterials in the cast cavity (2), letting it harden, and removing theformed implant and mandrel from the moulding material--one uses a pinprovided with a screw thread (fixing pin or screw) made of abiocompatible, but not osseo-integratable, material--e.g. high-qualitysteel--instead of the mandrel. Its diameter at the shaft is smaller thanthe diameter of the mandrel. In this way a gap is formed that one canfill with bioactive substances. In another design, the shaft of the pinprovided with a screw thread can be longer than the mandrel and itsscrew thread can cut the lowest point of the cast cavity (2). The fixingscrew, extended in this way and cutting its own screw thread, is screwedinto the jaw bone through the deepest point of the extraction socket.

If during the healing phase the biodegradable material is replaced bybone material under the effect of the biologically active material, thefixing screw is surrounded by bone material on all sides. Because thescrew is not osseo-integratable, it can be removed easily. The channelthat remains in the jaw bone makes possible the insertion of an exactlymatched fixture in its natural direction with respect to the axis. As analternative to this, one can leave a suitably formed osseo-integratablefixing screw in the jaw bone and provide it with an implantsuprastructure to use as a fixture.

The advantage of this variation is that an extraction and implantationcan be carried out with one therapeutic treatment. Through the presenceof biologically active substances on the surface of the implant anespecially effective wound closure of the bordering tissue takes place,as well as the quick osseo-integration of the implant fixture.

EXAMPLE 6

The object of variation (b) of the invention is described in greaterdetail below.

The cast cavity 2, e.g., an extraction socket, is reproduced in theabove-mentioned drawings. As an alternative to the design pictured withthe mandrels, one can use the extraction sockets or the extractionsockets shown in the moulding material of a porous matrix made ofsynthetic polymers or a natural material that contains biologicallyactive substances and fill the hollow spaces of this matrix with thehardening plastic material. Suitable synthetic polymer materials are,preferably, macrostructured and can be sponge-shaped forms with aperforated skeleton framework made of a polymer material, in which gapsconnecting under each other and pores are dispersed. Suitable materialsare, for instance, polycarbonates, polyorthoesters, PGA, PLA, ormixtures of them, etc. Such a design is especially suitable for adispensing unit that holds the biologically active substance to bedispensed in its polymer structure until it is dispensed.

A porous matrix made of natural material is, preferably, a dentinmatrix, which can be obtained by extracting teeth or tooth fragments.

EXAMPLE 7

The production of a dentin matrix from material suitable for a patientis described by way of example. One removes the cement and pulpmechanically according to the procedure described by K. Bessho, et al.,in the Journal of Dental Research 70 (1991), pp. 171-75. The toothmatter up to the size of a particle of approximately 1 mm³ is ground ina grinder. The ground material is washed in warm water, the oils removedby immersing it in a (1:1) chloroform/methanol solution for 12 hours,and the material is demineralized with a 0.5 molar HCl solution for 72hours at 4° C. Oils are again removed from the demineralized material 12hours long by immersing it in a (1:1) chloroform/methanol solution for 6hours, and then the material is treated for 24 hours in a 2-molarcalcium-chloride solution, for four hours in a 0.5 molar EDTA solutionat 7.4 pH, and for 24 hours in an 8-molar lithium-chloride solution, andthen washed in distilled water at 4° C. One extracts the materialpretreated in this way for 96 hours at 4° C. with a 20-fold volume of a4-molar guanidine-HCl solution. One centrifuges the extract (10,000 g.30 min. at 4° C.) and concentrates (1:5) the filtrate throughultrafiltration (Diaflo®-membrane YM-10; 10,000 mole weight fraction,Amicon Ireland). One adds to the concentrate three portions of ethanolcooled to -20°. The mixture is allowed to stand for 12 hours at 4° C.and centrifuged (10,000 g. 30 min. at 4° C.); and a concentrate thatcontains ethanol and an ethanolic residue is obtained. One washes theresidue with distilled water and dialyzes it with a 10-fold volume at 4°C. for 72 hours until the formation of the precipitate is completed,whereby the distilled water is changed every 12 hours. One centrifugesthe dialyzed residue (70,000 g. 30 min. at 4° C.) for the purpose ofdividing it into water-soluble and water-insoluble fractions,lyophilizes it, and determines the weight.

In the moulding material the reproduced cast cavity of an extractionsocket is filled with a mixture made of PGA/PLA copolymers and thematrix material that is made of dentin and contains BMP; and a rootimplant with fixture, which one inserts into the jaw bone at theintended site, is formed in the way already described above.

The invention is described herein by the written description, drawings,examples and the claims appended hereto. Variations and modifications ofthe invention will be apparent to one of ordinary skill in the art basedon a reading of these teachings. These variations and modifications areintended to be encompassed by the claims.

International patent application PCT/EP96/05506, filed Dec. 10, 1996 andSwiss patent application 3565/95, filed Dec. 18, 1995 are relied uponand incorporated herein by reference.

What is claimed is:
 1. A medical implant (5) for inserting into a spacewith a pre-specified dimension and for filling a cast cavity (2) with ahardening plastic material with mineral components on the basis ofcalcium and phosphate or, in the case of the new formation of bone, abiodegradable material, or a combination of both, which is obtainedby:a) placing at least one mandrel (3; 23, 24) in the cast cavity (2) insuch a way that it can be removed from the cast cavity (2) of the formedimplant (5) after the plastic material hardens and creating, with theremoval of the mandrel, a space (6; 19) that extends from the inner areaof the implant (5) to the outer surface, thus forming a reservoir thatcan be filled with a biologically active substance, or b) filling thecase cavity (2) with a porous matrix and a biologically activesubstance, and the hollow spaces of this matrix with the hardeningplastic material.
 2. A medical implant (5) according to claim 1, whichis obtained by forming the cast cavity (2) as an impression of anextracted tooth.
 3. A medical implant according to claim 1, which isobtained by using mandrels designed as filament-shaped or rod-shapedmandrels (3) and forming the reservoirs as channel-shaped orcapillary-shaped spaces.
 4. A medical implant according to claim 1,which is obtained by using, for the biodegradable material, anosteo-conductive polymer.
 5. A medical implant according to claim 1,which is obtained by filling, as a biologically active substance, anactive ingredient with osteo-inductive properties.
 6. A medical implantaccording to claim 1, which is obtained by filling the reservoir with abiologically active substance, a protein with the properties of atransforming growth factor of the type beta (TGF-β) or combinations ofthem.
 7. A process for the production of a medical implant (5), whichcomprises forming a cast cavity (2) in molding material (1) in the formof an impression of an extracted tooth or resected bone;filling thiscast cavity (2) with a hardening material with mineral components on thebasis of calcium or phosphate, or a biodegradable material; placing atleast one mandrel (3; 23; 24) in the cast cavity in such a way that itcan be removed from the cast cavity of the formed implant (5) after theplastic material hardens; creating with the removal of the mandrel aspace (6; 19) that serves as a reservoir and extends from the inner areaof the implant (5) to the outer surface; removing the formed implant (5)from the cast cavity and, after removing the mandrels (3; 23; 24),filling the reservoir with a biologically active substance.
 8. A processaccording to claim 7, which comprises inserting an alloplastic,osseo-integratable fixture in the cast cavity (2).
 9. A processaccording to claim 7, which comprises first inserting into the castcavity (2) several mandrels (3; 23, 24), which run from the cast cavity(2) to the molding material (1) and are arranged in such a way that oneremoves the mandrels (3; 23, 24) from the implant after filling the castcavity (2) with the plastic molding material, letting it harden, andremoving the formed implants (5) from the cast cavity (2).
 10. A processaccording to claim 7, which comprises producing a medical implant as adispensing unit for biologically active substances.